gms | German Medical Science

Objective: Meningiomas, mostly benign tumors that arise from the meninges, can be associated with headaches. The origin of these secondary headaches is unknown; the size of the tumor is not a crucial factor for the occurrence of headaches. We asked whether neuropeptides like substance P (SP) or calcitonin gene-related peptide (CGRP) and their receptors, as well as histamine and prostaglandin E2 (PGE2), which are related to nociceptive processes, occur in painful meningiomas at increased levels.

Method: In a sample of 60 meningiomas, SP, PGE2, histamine and CGRP were determined with enzyme-linked immunosorbent assay (ELISA) relative to the weight of the tissue and the content of protein. As a first step we compared meningiomas with high and low contents of SP. Each tissue was immunohistochemically (IHC) processed using antibodies for SP, NK-1 receptors and the CGRP receptor components CLR and RAMP-1. The immunofluorescence of secondary antibodies was evaluated with confocal laser microscopy. In addition we examined the presence of NK-1 receptor protein in selected meningiomas by Western blot. Patients were asked to answer a questionnaire about their headaches before and after the operation.

Results: The concentration of SP in the examined meningiomas varied between 3 and 424 pg/mg with an average of 40.6 pg/mg. The tumors contained high amounts of PGE2 (mean 6341 pg/mg) but little CGRP (mean 12.6 pg/mg) and nearly no histamine. The IHC examination showed in most cases a positive immunofluorescence for SP and NK-1 receptors, whereas only half of the investigated tissues were immunopositive for CLR and RAMP-1. The presence of NK-1 receptors could be detected by Western blot. 49% of the patients showed a positive headache anamnesis and 32% did not complain about pain in general; 19% of the patients did not provide information. Meningiomas of patients with a positive headache anamnesis contained considerably more SP with an average of 139.2 pg/mg compared to patients who did not suffer from headaches with an average of 58.7 pg/mg.

Conclusions: The results from the ELISA and the IHC showed a predominance of SP and NK-1 expression in most of the tumors. The content of SP in meningiomas seems to be associated with a higher prevalence of headaches. Expression of NK-1 receptors was also found in the endothelium of blood vessels, which is in agreement with vascular functions of SP.